Cell Signalling in Health and Disease - Proteasome

Question 1

where are some ubiquitinated proteins targeted to

Answer 1

proteasomes

Question 2

function of chaperone proteins

Answer 2

catalyse the folding of proteins into their native state

Question 3

features of chaperone proteins

Answer 3

can be ATP-dependent/independent
variety of catalytic mechanisms

Question 4

how are chaperones usually classified

Answer 4

classed according to their molecular weight

Question 5

function of holdases

Answer 5

holdases are chaperones that form reversible complexes with proteins in their misfolded conformations to maintain their solubility
ATP-independent

Question 6

function of foldases

Answer 6

chaperones that assist in the folding in proteins
ATP-dependent

Question 7

function of unfoldases/disaggregases

Answer 7

chaperones involved in unfolding aggregated proteins
usually ATP-dependent

Question 8

what is the transition state and its purpose after a nucleophilic attack

Answer 8

tetrahedral intermediate
makes it very unstable and allows it to leave the proteosome
acts as a leaving group

Question 9

what are the 4 different types of proteolytic mechanisms

Answer 9

metalloprotease
serine
cystine
threonine

Question 10

how does the proteosome cleave peptide bonds

Answer 10

uses 3 sets of two threonine protease active sites

Question 11

what are the function of immunoproteosomes

Answer 11

sample the ‘trash can’ of a cell and post peptides on MHC I
basically detects foreign protein at the level of degradation

Question 12

what does protein folding quality in the ER require

Question 13

what is the function of proteosomes in the cell cycle

Answer 13

mainly to degrade cyclins

Question 14

what is the 20s core particle

Answer 14

a structure in the proteosome - barrel shaped proteolytic core complex
capped at one or both ends by a 10s regulatory complex
recognises ubiquitinated proteins

Question 15

what does the proteosome require to cleave proteins and why

Answer 15

uses 3 sets of two threonine protease active sites
allows the protease to recognise more proteins

Question 16

what does the final stage of proteosome specificity rely on

Answer 16

depends on the precise fit of substrate into beta subunit sites

Question 17

function of immunoproteosomes

Answer 17

act as the trash can of the cell
display peptides on MHC I

Question 18

how does the herpes virus use proteosomal degradation to evade the immune system

Answer 18

use proteins US2 and US11 to trigger the retro-translocation of MCH I

Question 19

how does the cholera toxin use proteasomal degradation to evade the immune system

Answer 19

uses retro-translocation to machinery to evade the ER and fold into the cytoplasm

Question 20

what is the process of ubiquitination dependent on

Answer 20

ATP-dependent process carried out by 3 classes of enzymes

Question 21

what is the bond between ubiquitin and protein

Answer 21

iso-peptide bond

Question 22

what are E1 enzymes

Answer 22

ubiquitin activating enzymes

Question 23

how do E1 enzymes perform their function

Answer 23

form a thioester bond to the carboxyl end of ubiquitin
ATP-dependent

Question 24

what are E2

Answer 24

ubiquitin-conjugating enzymes

Question 25

how does E2 perform its function

Answer 25

activated ubiquitin via E1 is transferred to cystine residues of E2

Question 26

what are E3

Answer 26

ubiquitin-ligase enzymes

Question 27

what is the function of E3

Answer 27

transfer the ubiquitin to the target protein

Question 28

outline the 3 step ubiquitination conjugation mechanism

Answer 28

ubiquitin is bound to the carboxyl group of a protein in the presence of ATP E1 binds the carboxyl group forming an unstable thioester intermediate E2 then replaces E1 by binding its cysteine group the the thioester bond E3 then binds ubiquitin and ligases it the target protein